Abstract
Fibroblast growth factor receptor 1 (FGFR1) has been suggested to be the candidate gene for 8p11–12 amplification in breast cancer and its therapeutic/prognostic value is explored. Most previous studies focused on FGFR1 gene amplification, which may not necessarily lead to protein expression. Therefore, analysis of protein level may have more clinical relevance. We evaluated FGFR1 expression in a large cohort of breast cancer by immunohistochemistry, correlated with the tumor clinic-pathologic features, biomarkers expression, and patient's survival. FGFR1 expression was associated mainly with luminal cancers, particularly luminal B subtype (23.5%; p < 0.001), and it also showed adverse prognostic impact on luminal A cancers. FGFR1 expression was associated with higher pN (p = 0.023), pT (p = 0.003) stages, lymphovascular invasion (p = 0.010), p-cadherin (p = 0.028), synaptophysin (p = 0.009) and SOX2 expression (p = 0.034) in luminal A cancers. FGFR1 expressing luminal A cancers showed a similar outcome as luminal B cancers. Multivariate Cox regression analysis demonstrated FGFR1 positive luminal A cancers to be an independently poor prognosticator for disease free survival in luminal cancers (hazard ratio = 3.341, p = 0.008). Thus FGFR1 could be useful in identifying the aggressive cases amongst heterogeneous luminal A cancers. Given the relevance of FGFR pathway in treatment resistance in luminal cancers, FGFR1 could be an important tumor biomarker and adverse prognostic factor potentially exploitable in the clinical management of luminal cancers.
Highlights
Breast carcinogenesis may involve genetic alterations including activation or amplification of oncogenes [1]
Fibroblast growth factor receptor 1 (FGFR1) expression was found to be associated with high pN (p = 0.042), pT (p = 0.037) stages and large tumor size (p = 0.017), but not with tumor grade, Lymphovascular invasion (LVI), fibrotic focus (FF) and patients’ age (Table 1)
Significant difference in FGFR1 expression was found among different molecular subtypes (p < 0.001), with the highest expression rate seen in Luminal B (Lum B) cancers (Table 1)
Summary
Breast carcinogenesis may involve genetic alterations including activation or amplification of oncogenes [1]. FGFR1 plays critical functions in the normal mammary physiologic development and tissue homeostasis. It is expressed in the mammary epithelium during ductal morphogenesis. Aberrant FGFR regulation or expression induced mammary tumor cell proliferation, anti-apoptosis, drug resistance, epithelial-to-mesenchymal transition (EMT) and invasion [6, 7]. FGFR1 amplification was associated with distant metastasis, early relapse and poor survival [3, 9,10,11], and contributed to poor prognosis in luminal breast cancers by driving anchorage independent proliferation and endocrine therapy resistance [10]. It was important to note that FGFR1 gene amplification did not necessarily lead to a high protein expression, as low protein expression level in FGFR1 amplified tumors had been observed [10]
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